肝X受体激动剂对抑郁模型小鼠海马少突胶质细胞的影响

Effects of LXRs agonist on hippocampal oligodendrocytes in the CUS mouse model of depression

目的:探讨肝X受体(LXRs)激动剂(GW3965)对慢性不可预知性应激(CUS)诱导的抑郁症小鼠海马结构各亚区内少突胶质细胞数量的影响。方法:将51只4〜6周龄雄性C57BL/6J小鼠,随机分为对照组(control)、慢性不可预知性应激组(CUS)和慢性不可预知性应激+GW3965处理组(CUS+GW3965),给予CUS组小鼠和CUS+GW3965组小鼠连续70 d的CUS干预,同时从第43 d起给予CUS+GW3965组小鼠连续28 d的腹腔注射GW3965,在第70 d进行行为学测试,随后利用免疫组织化学结合现代体视学方法,对小鼠海马结构各亚区CC1+标记的成熟少突胶质细胞的数量进行三维定量研究。结果:42 d的CUS干预导致CUS组小鼠和CUS+GW3965组小鼠的体质量和糖水偏好百分比均显著性降低,强迫游泳不动时间显著性增加;而28 d的LXRs激动剂治疗可显著性增加CUS+GW3965组糖水偏好百分比,并显著性减少强迫游泳不动时间。体视学结果显示:CUS干预可导致小鼠海马CA 1区、CA 3区和D G区内CC1^(+)少突胶质细胞数量显著性减少,而LXRs激动剂治疗可显著增加CUS+GW3965组小鼠海马CA3区内CC1^(+)少突胶质细胞数量。结论:LXRs激动剂能够改善CUS模型小鼠的抑郁样症状,逆转抑郁症模型小鼠海马CA 3区内少突胶质细胞的丢失。

Objective: To investigate the effects of liver X receptors( LXRs) agonists( GW3965) on oligodendrocytes in the hippocampal subregions of the depressed model mice which were induced by chronic unpredictable stress( CUS). Methods: Fifty-one male C57 BL/6 J mice aged 4-6 weeks were randomly divided into control group,CUS group and CUS + GW3965 group. The CUS group and the CUS + GW3965 group were subjected to CUS procedure for 70 consecutive days. Meanwhile,the CUS + GW3965 group was intraperitoneally injected with GW3965 from the day 43.Behavioral tests were performed on the day 70 and then the numbers of the CC1 positive oligodendrocytes in hippocampal subregions were quantitatively investigated using immunohistochemical technique and the modern stereological methods.Results: After 42 days of CUS intervention,compared with the control group,the body weight and the percentage of sucrose consumption of mice in the CUS group and the CUS + GW3965 group were significantly reduced,and the immobility time in forced swimming test with the CUS group mice was significantly increased. After 28 days of drug intervention with GW3965,the percentage of sucrose consumption of the CUS + GW3965 group was significantly higher than that of the CUS group,and the forced swimming immobility time was significantly lower than that of the CUS group. The stereological results showed that compared with the control group,the numbers of CC1+cells in CA1,CA3 and DG of the CUS group were significantly reduced,while the number of CC1+cells in CA3 of the CUS + GW3965 group was significantly higher than those of CUS group. Conclusion: LXRs agonist could reverse the depression-like behaviors and protect the oligodendrocytes in the hippocampus CA3 region of the CUS mice,which might be one of the important structural bases for the antidepressant treatment of LXRs agonist.